Sodium Glucose Co-transporter (SGLT) Inhibitors in Nonobstructive Hypertrophic Cardiomyopathy

NCT ID: NCT06433050

Last Updated: 2025-01-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-17
• Study Completion Date: 2027-06-30

Brief Summary

The goal of this clinical trial is to learn if sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, works to treat symptomatic, nonobstructive hypertrophic cardiomyopathy (noHCM) in adult patients. It will also learn about the safety of sotagliflozin in this patient population. The main questions it aims to answer are:

1. Will sotagliflozin be well tolerated in patients with nonobstructive HCM?

2. Will sotaglifozin improve exercise capacity, diastolic dysfunction and/or physical functioning in patients with nonobstructive HCM?

3. Will sotagliflozin improve circulating markers of cardiac metabolism in patients with nonobstructive HCM?

Researchers will compare sotagliflozin to a placebo (a look-alike substance that contains no drug) to see if sotagliflozin is effective at treating hypertrophic cardiomyopathy (HCM).

Participants will:

Take sotagliflozin or a placebo every day for 12 weeks. They will then cross-over (or switch) to taking placebo or sotagliflozin (whichever one they did not take initially) for an additional 12 weeks.

Visit the clinic once every 4-12 weeks for checkups, surveys, and tests including a stress test and echocardiogram.

Conditions

Hypertrophic Cardiomyopathy Without Obstruction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo first phase, Sotagliflozin second phase

Matching placebo once daily will be administered in the first phase, Sotagliflozin 400 mg once daily will be administered in the second phase

Group Type: PLACEBO_COMPARATOR

Sotagliflozin

Intervention Type: DRUG

Sotagliflozin or placebo will be administered to each participant in a cross over study design. Each participant will receive active drug and placebo with randomization of the order in which they receive them.

Sotagliflozin first phase, Placebo second phase

Sotagliflozin 400 mg once daily will be administered in the first phase, matching placebo once daily will be administered in the second phase

Group Type: ACTIVE_COMPARATOR

Sotagliflozin

Intervention Type: DRUG

Sotagliflozin or placebo will be administered to each participant in a cross over study design. Each participant will receive active drug and placebo with randomization of the order in which they receive them.

Interventions

Sotagliflozin

Sotagliflozin or placebo will be administered to each participant in a cross over study design. Each participant will receive active drug and placebo with randomization of the order in which they receive them.

Intervention Type: DRUG

Other Intervention Names

Inpefa

Eligibility Criteria

Inclusion Criteria

1. Age at least 18 years, both sexes

2. Provision of signed and dated informed consent form

3. Stated willingness to comply with all study procedures and availability for the duration of the study

4. Ability to take oral medication and be willing to adhere to the study intervention.

5. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 2 weeks after the end of administration of study drug.

6. Diagnosis of HCM with NYHA Class II-III functional class or New York Heart Association (NYHA) Class I with peak VO2 < 90% on cardiopulmonary exercise stress testing performed at Visit 1.

7. Left ventricular outflow tract gradient < 50 mmHg at rest, with valsalva, and with exercise.

7. Left ventricular ejection fraction > 50% by echocardiogram or cardiac MRI based on the most recent assessment in the past year prior to screening and confirmed during Visit 1 echocardiogram.

8. Stable medical therapy for at least 1 month prior to study enrollment.

Exclusion Criteria

1. Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrollment or previous intolerance of an SGLT2 inhibitor

2. Type 1 diabetes mellitus

3. Age <18 years old

4. Pregnant or lactating women: Women of childbearing potential will undergo a urine pregnancy test during the screening visit.

5. Uncontrolled atrial fibrillation, as defined by a resting heart rate > 100 beats per minute at the time of the baseline assessment

6. Paroxysmal atrial fibrillation (Afib) or flutter with plans to attempt to restore sinus rhythm (with drug therapy, ablation, or DC cardioversion) during the study period.

7. Unable to attain a respiratory exchange ratio of at least 1.05 on cardiopulmonary exercise test (CPET) on the day of screening.

8. Septal reduction therapy within the previous 3 months.

9. Implantable cardio-defibrillator (ICD) implantation planned during the study period.

10. Implantation of a cardiac resynchronization therapy (CRT) device within 12 weeks prior to enrollment or intent to implant a CRT device during the study period

11. Hemoglobin < 10 g/dL

12. Estimated glomerular filtration rate (eGFR) < 25 mL/min/1.73m^2, or unstable or rapidly progressing renal disease at the time of randomization

13. Subject inability/unwillingness to exercise

14. Greater than moderate left sided valvular disease (mitral regurgitation, aortic stenosis, aortic regurgitation), moderate or greater mitral stenosis, or severe right-sided valvular disease based on baseline echo at the time of enrollment

15. Current angina due to clinically significant epicardial coronary disease, as per investigator judgment

16. Acute coronary syndrome or coronary intervention within the past 2 months

17. Primary pulmonary artery hypertension (WHO Group 1 Pulmonary Arterial Hypertension)

18. Clinically significant lung disease as defined by: Chronic Obstructive Pulmonary Disease meeting Stage III or greater GOLD criteria (FEV1<50% predicted), treatment with oral steroids within the past 6 months for an exacerbation of obstructive lung disease, or current use of supplemental oxygen aside from nocturnal oxygen for the treatment of obstructive sleep apnea.

19. Clinically-significant ischemia, as per investigator's judgement, on stress testing without either (1) subsequent revascularization, (2) an angiogram demonstrating the absence of clinically significant epicardial coronary artery disease, as per investigator judgment; (3) a follow-up 'negative' stress test, particularly when using a more specific technique (i.e., a negative perfusion imaging test following a 'positive' ECG stress test)

20. Symptomatic bradycardia or second- or third-degree heart block, in the absence of a pacemaker

21. Significant liver disease impacting synthetic function or volume control (ALT/AST > 3x ULN, Albumin < 3.0 g/dL)

22. Severe right ventricular dysfunction on baseline echocardiogram

23. Orthostatic blood pressure response to the transition from supine to standing (>20 mmHg reduction in systolic blood pressure 2-3 minutes after standing)

24. Active participation in another study that utilizes an investigational agent (observational studies/registries allowed)

25. Any condition that, in the opinion of the investigator, will interfere with the completion of the study. This may include comorbid or psychiatric conditions that may impede successful completion of the protocol, or logistical concerns (e.g. inability to travel to the exercise unit).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Sharlene Day

Associate Professor of Cardiovascular Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sharlene Day, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sharlene Day, MD

Role: CONTACT

sharlene.day@pennmedicine.upenn.edu

734-548-0394

Kim Clinton

Role: CONTACT

kimberly.clinton@pennmedicine.upenn.edu

215-431-4545

Facility Contacts

Sharlene Day, MD

Role: primary

sharlene.day@pennmedicine.upenn.edu

734-548-0394

Lindsey Behlman

Role: backup

lindsey.behlman@pennmedicine.upenn.edu

Other Identifiers

R61HL164376

Identifier Type: NIH

Identifier Source: secondary_id

View Link

855065

Identifier Type: -

Identifier Source: org_study_id